Alterations in neuropeptide expression in lumbosacral bladder pathways following chronic cystitis

These studies examined changes in the expression of calcitonin gene-related peptide (CGRP) and substance P (SP) in lumbosacral (L6-S1) micturition ref lex pathways, following chronic cystitis induced by cyclophosphamide (CYP). In control Wistar rats, CGRP- or SP-immunoreactivity (IR) was expressed in fibers in the superficial dorsal horn in all segmental levels examined (L4 -S1). Bladder efferent cells in the dorsal root ganglia (DRG; L6, S1) from control animals also exhibited CGRP(41-55%) or SP-IR (2-3%). Following chro nic. CYP-induced cystitis, CGRP- and SP-IR were dramatically increased in s pinal segments and DRG (L6, S1) involved in micturition reflexes. The densi ty of CGRP- and SP-IR was increased in the superficial laminae (I-II) of th e L6 and S1 spinal segments. No changes in CGRP- or SP-IR were observed in the L4-L5 segments. Staining was also dramatically increased in a fiber bun dle extending ventrally from Lissauer's tract in lamina I along the lateral edge of the DH to the sacral parasympathetic nucleus in the L6-S1 spinal s egments. Following chronic cystitis. CGRP- and SP-IR in cells in the L6 and S1 DRG significantly (P less than or equal to 0.05) increased and the perc entage of bladder afferent cells expressing CGRP- (76%) or SP-IR(11-18%) al so significantly (P less than or equal to 0.001) increased. No changes were observed in the L4-L5 DRG. These studies suggest that the neuropeptides, C GRP and SP, may play a role in urinary bladder afferent pathways, following chronic urinary bladder inflammation. Changes in CGRP or SP expression fol lowing cystitis may contribute to the altered visceral sensation (allodynia ) and/or urinary bladder hyperreflexia in the clinical syndrome. interstiti al cystitis. (C) 2001 Elsevier Science B.V. All rights reserved.